Detection system and method for aerosol delivery

ABSTRACT

An apparatus comprises a detector, a pressure sensor and a processor. The detector is operable to detect light that is scattered by an aerosol that is associated with a pressure. The pressure sensor is operable to measure the pressure. The processor is coupled to the detector and to the pressure sensor, and is configured to receive at least a signal from the detector and the pressure sensor. The processor is further configured to use the received signals to calculate a volume of the first aerosol, and to output an output signal associated with the calculated volume. The various measurements can be repeated and compared, and the output signal can be a feedback signal for metering subsequent amounts of the aerosol, based on the comparison.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/437,306, filed May 7, 2009, and entitled “Detection System and Methodfor Aerosol Delivery” (H22), which is a continuation of U.S. patentapplication Ser. No. 12/045,386, filed Mar. 10, 2008, and entitled“Detection system and Method for Aerosol Delivery” (F13), now U.S. Pat.No. 7,548,314 issued Jun. 16, 2009, which is a continuation of U.S.patent application Ser. No. 10/675,278, filed Sep. 30, 2003, andentitled “Detection System and Method for Aerosol Delivery” (D41), nowU.S. Pat. No. 7,342,660 issued Mar. 11, 2008, which is acontinuation-in-part of U.S. patent application Ser. No. 10/670,655,filed Sep. 25, 2003, and entitled “Detection System and Method forAerosol Delivery” (D42), now abandoned, all of which are incorporatedherein by reference in their entireties.

NOTICE OF COPYRIGHT PROTECTION

A section of the disclosure of this patent document contains materialsubject to copyright protection. The copyright owner has no objection tothe facsimile reproduction by anyone of the patent document, butotherwise reserves all copyright rights whatsoever.

TECHNICAL FIELD

The present invention generally relates to systems and methods formeasuring quantities of aerosolized compounds. More particularly,embodiments of the present invention can relate to systems and methodsfor accurately delivering atomized substances, such as therapeuticagents.

BACKGROUND INFORMATION

A variety of substances, such as therapeutic agents, may be delivered byinhalation, including aerosolized liquids and powder drugs, for thetherapeutic treatment of the lungs and inhalation passageways and/or forthe delivery of systemic agents. The inhalation of systemic therapeuticagents is considered a potential alternative to injections and othertypes of drug delivery systems. For example, insulin may be delivered byinhalation in aerosolized form, thus avoiding the need for the injectionof insulin into a patient,

Inhaling aerosols, however, typically lacks the accuracy of injections,and so may be inappropriate for use in situations where accurate dosingis critical with aerosolized drugs, the proper amount; required fordelivery is often not properly metered for delivery. For example, asthmainhalers typically have an acceptable accuracy of plus or minus 25% ofthe nominal dose. For systemic drug delivery of insulin, on the otherhand, such a level of accuracy is considered too unpredictable to allowfor appropriate use, even though aerosolized delivery may be preferableto intravenous delivery for a variety of reasons.

Thus, a need exists for accurately and predictably delivering apredetermined dose of aerosolized drugs.

SUMMARY

An embodiment comprises a light detector, a pressure sensor and aprocessor. The light detector is operable to detect light that isscattered by an aerosol that is associated with a pressure. The pressuresensor is operable to measure the pressure. The processor is coupled tothe light detector and to the pressure sensor, and is configured toreceive at least a signal from the detector and the pressure sensor. Theprocessor is further configured to use the received signals to calculatea volume of the first aerosol, and to output, a signal associated withthe calculated volume.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a system for delivering aerosolaccording to an embodiment of the invention.

FIG. 2 is a block diagram of a light scatter detector according to anembodiment of the invention.

FIG. 2A is a block diagram of a light scatter detector including a beamdump, according to an embodiment of the invention.

FIG. 3 is a schematic diagram of a system for delivering aerosolaccording to an embodiment of the invention.

FIG. 4 is a block-diagram of a method of measuring the physicalcharacteristics of an aerosol according to an embodiment of theinvention.

FIG. 5 is a block diagram of a method of measuring the physicalcharacteristics of an aerosol according to an embodiment of theinvention.

FIG. 6 is a schematic diagram of a system for delivering aerosolaccording to an embodiment of the invention.

DETAILED DESCRIPTION

Embodiments of the invention include systems and methods for measuring,analyzing, and metering aerosols. For purposes of this application, theterm aerosol includes airflows containing particles, such as aerosolizedliquids, powders, and combinations of these, as well as airflows that donot contain any aerosolized particles. One use for the invention is as areal time aerosol volume transducer. With this use, aerosol density (forexample, aerosol particles per liter) in a system can be measured bylight scatter. If airflow (for example, liters per second) is alsodetermined, then these two parameters multiplied together yield thenumber of aerosol particles per second passing through the chamber. Thenumber of particles per second can then be integrated to calculate thetotal number of aerosol particles (i.e. volume) that passed through thesystem. The volume measurement can be repeated, and a comparison ofvolume measurements can be fed back to a system to, for example, metersubsequent amounts of aerosol.

FIG. 1 shows a block diagram of a contextual overview for employingembodiments of the present invention. In this overview, a substance,which can be a liquid or solid form of a therapeutic agent, or which canbe any liquid or solid capable of being converted to an aerosol, iscontained in aerosol selector 101. Aerosol selector 101 includesatomizer 102, and is coupled to aerosol flow path 103 such that anaerosol can be introduced from atomizer 102 into aerosol flow path 103.For purposes of the application, the term atomizer includes any deviseor component that is capable of producing an aerosol from solids,liquids, or any combination thereof.

In one embodiment of the invention, aerosol flow path 103 includes alight source 104, a light detector 105 and a pressure sensor 107. Lightdetector 105 and pressure sensor 107 are coupled to processor 106.Processor 106 can be configured to receive a signal from light detector105 and a signal from pressure sensor 107. The respective signals can besent to processor 106 in substantially real time, or in some way thatassociates the respective signals.

Processor 106 can be further configured to calculate a volume of thefirst aerosol, the calculation being based on the signal received fromlight detector 105 and on the signal received from pressure sensor 107.In one embodiment, processor 106 can calculate aerosol volume byreceiving a signal from detector 105 that is associated with aerosoldensity, receiving a signal from pressure sensor 107 that is associatedwith pressure or flow rate, and multiplying the aerosol density (i.e.,number of particles per unit volume) by the pressure or flow rate. Theresult is a representation of the number of particles per second thattraverses aerosol flow path 103, or that traverses some subvolume ofaerosol flow path 103. The number of particles per second can then beintegrated over time to calculate the total number of aerosol particles(i.e. volume) that passed through the system.

Alternatively, airflow can be measured in a variety of way other thanutilizing pressure sensor 107. For example, airflow can be measured by aturbine-type meter or a hot-wire anemometer.

In one embodiment, processor 106 can be configured to repeat the volumecalculation for aerosols that are subsequently introduced into aerosolflow path 103, and compare previous and subsequent volume calculations.The comparison can be used to create a feedback signal, output fromprocessor 106 and received by aerosol selector 101, for meteringsubsequent aerosols.

In another embodiment, processor 106 is configured to receive a firstsignal and a second signal from light detector 105. The first signal isassociated with light scattering from a first aerosol that is associatedwith a first pressure. For the purposes of the invention, the phrase“first aerosol” means an aerosol with distinct properties such ascomposition, number of particles per unit volume, and particle size. Thesecond signal is associated with light scattering from a second aerosolthat is associated with a second pressure. For the purposes of theinvention, the phrase “second aerosol” means an aerosol with a number ofparticles per unit volume, a particle size or a general composition thatmay or may not be different from the first aerosol.

One skilled in the art will understand that the first pressure and thesecond pressure may or may not be the same pressure, and may or may notoccur in the same region, or in different regions that have the samegeneral geometry.

In one embodiment, the first aerosol is a medicine to be inhaled, thefirst pressure is associated with inhalation, and the second pressure isassociated with exhalation. In other embodiments, the first and secondpressures can be from sources not associated with inhalation andexhalation. Processor 106 is further configured to output an outputsignal associated with a comparison of the first signal and the secondsignal. For the purposes of the invention, the term “comparison” mayinclude any measure of difference between the first aerosol and thesecond aerosol. For example, the comparison may include subtracting thenumber of particles per unit volume in the first aerosol from the numberof particles per unit volume in the second aerosol. Alternatively, thecomparison may include, for example, determining the ratio of suchnumbers of particles, or comparing input particle size to outputparticle size. In one embodiment, breath pause timing can be measured.

The output signal can be fed back to aerosol selector 101 to improve,refine, or otherwise assist in any function performed by aerosolselector 101. In addition, the output signal can be used to alter theuser's flow pattern for optimal deposition. For example, the outputsignal can contain information used to indicate to a patient to breathlonger, deeper, shorter and/or shallower.

In one embodiment, aerosol selector 101 can receive the output signal,and can use the information contained in the output signal to meter athird aerosol. For the purposes of the invention, the term “thirdaerosol” means an aerosol with a number of particles per unit volume, aparticle size, or a general composition that may or may not be differentfrom the first aerosol. In another embodiment, the output signal caninclude comparison information to assist in metering subsequent dosessuch that the total dose delivered to a patient can be delivered inpredictable and/or measurable quantities.

Light source 104 can be a laser, or any light source that is practicablefor the present invention. For example, light source 104 can be a lightemitting diode (with or without a collimator), or can be a fluorescenceof the aerosol itself. Light from light source 104 can be polarizedand/or collimated in such a way that, after scattering from the aerosol,the light can be detected in detector 105. Light detector 105 can be anylight detector, or multiple light detectors, or an array of lightdetectors, or any combination of light detectors in any geometryoperable to detect scattered light, and to send a signal to processor105. For example, light detector 105 can be any practicable number andcombination of photomultiplier tubes, CCDs, silicon photodetectors,pyroelectric detectors, etc. Examples of appropriate geometries includeconcentric circles, grid patterns, or any geometry practicable for thepurposes of a particular measurement. For the purposes of the presentinvention, the term “scatter” includes, but is not limited to,scattering due to diffraction.

For the purposes of the invention, the term processor includes, forexample, any combination of hardware, computer programs, software,firmware and digital logical processors capable of processing input,executing algorithms, and generating output as necessary to practiceembodiments of the present invention. Such a processor may include amicroprocessor, an Application Specific Integrated Circuit (ASIC), andstate machines. Such a processor can include, or can be in communicationwith, a processor readable medium that stores instructions that, whenexecuted by the processor, causes the processor to perform the stepsdescribed herein as carried out, or assisted, by a processor.

For the purposes of the invention, “processor readable medium,” orsimply “medium,” includes but is not limited to, electronic, optical,magnetic, or other storage or transmission devices capable of providinga processor with processor readable instructions. Other examples ofsuitable media include, but are not limited to, a floppy disk, CD-ROM,magnetic disk, memory chip, ROM, RAM, ASIC, configured processor, alloptical media, all magnetic tape or other magnetic media, or any othermedium from which a processor can read. Also, various other forms ofprocessor readable media may transmit or carry instructions to acomputer, including a router, private or public network, or othertransmission device or channel. Also, various other forms of processorreadable media may transmit or carry instructions to a computer,including a router, private or public network, or other transmissiondevice or channel.

Aerosol flow path 103 can further include a region of variable pressureresistance 108, and a region of fixed pressure resistance 109.

FIG. 2 shows a block diagram of a light scatter detector according to anembodiment of the invention. In this embodiment, light source 201 iscoupled to scatter chamber 202 by aperture 203. Light source 201 can be,for example, a laser diode emitting a laser beam. Aperture 203 isconfigured to remove stray light emitted by the laser diode, and has alength that provides room for properly focusing the laser beam withinscatter chamber 202. The laser beam can exit the chamber throughaperture 204 in light detector 205.

When light passes through the aerosol, the light can scatter away fromthe optical path. Accordingly, scatter chamber 202 can be a polishedaluminum tube, or can be any material that allows scattered light to bedirected toward light detector 205.

Because air and vapor do not scatter as much light as an aerosol, theamount of light scattered depends largely on the density of theaerosolized particles in the light path. Thus, knowledge of the airflowrate, provided by a pressure sensor, and the amount of light scatteredfrom a laser beam, allows the mass flow of aerosol to be determined.Ideally, the amount of light scattered by a monodispersed aerosol isrepresented by the following equation:I.sub.m=I.sub.0(1-e.sup.-.alpha..r-ho.)+I.sub.DC. In this equation, thevariables I.sub.m, I.sub.0, and I.sub.DC are the measured intensity, theincident intensity, and the background intensity. The variable .alpha.,with units of m.sup.3, is a coefficient converting the density ofscatterers, .rho., having units of #scatterers/m.sup.3, into theprobability that a photon will pass through the chamber withoutscattering. The coefficient .alpha. is essentially independent of allfactors except for physical characteristics of the aerosol and thegeometry of the chamber. When the aerosol is sufficiently similar to thecalibration standard, the measured intensity only depends upon theamount of incident light, the background light, and the density ofscatters.

Again ideally, the density of scatterers is given by.rho.=.gamma.(.mu..sub.m/Q), where .mu..sub.m is the volume flow rate ofthe aerosolized particles .mu.L/s, Q is the volume flow rate of air,L/s, and .gamma. is a coefficient relating mass of the aerosolizedparticles to the number of scattering particles. The coefficient .gamma.has units of L/.mu.Lm.sup.3.

To solve for .mu..sub.m,.mu..sub.m=(-Q/.alpha..gamma.)[ln(I.sub.0+-I.sub.DC-I.sub.m)-ln(I.sub.0)].This equation provides a nominal functional relation between aerosolmass flow, airflow, and measured intensity. In practice, of course,embodiments of the system exhibit non-ideal and non-linear behavior.These behaviors can be based on (i) a non-zero width of the laser beam;(ii) a non-constant velocity profile of the airflow and aerosoldistribution; (iii) a polydispersed aerosol; and (iv) volatility of theaerosol.

Thus, the volume flow rate of the aerosolized particles may retain theform .mu.m=f(Q{ln(I.sub.0+I.sub.DC-I.sub.m)-ln(I.sub.0)}). Toaccommodate for non-linearities, the following cubic approximation tothe true functional relation may be used: 1 m=i=1 3 a i {Q[ln(I 0+I DC-Im)-ln(I 0)]}i.

This relation and its coefficients absorb the product .alpha.gamma.

The coefficients a.sub.i can be determined in a number of ways,including through the use of a standard least-squares algorithm tominimize the difference between predicted mass flow and mass flowmeasured from a calibrated aerosol or a test strip with a calibrationscattering coefficient

In one embodiment, light source 201 can be modulated with an on-offsquare beam to improve the signal to noise ratio. In this embodiment,the detector signal is integrated during the on period, S.sub.1, andseparately during the off period, S.sub.0. The signal used to calculateaerosol volume is thus the difference, S.sub.1-S.sub.0. To implementthis embodiment, the system is configured such that the baseline noisefrom the detector and any ambient light are likely captured by theoff-period signal. In other embodiments of the invention, othermodulation techniques can be used to improve the signal to noise ratio.

FIG. 2A is a block diagram of a light scatter detector including a beamdump according to an embodiment of the invention. In this embodiment,light source 201 a emits light into scatter chamber 202 a. Detector 203a contains an aperture (not numbered), so that when light from lightsource 201 a exits the aperture, it illuminates beam dump 204 a. Beamdump 204 a is in the direct path of the light beam, and is configured toabsorb or contain light that is not scattered by the aerosol. In oneembodiment, beam dump 204 a is simply a hole allowing the light beam toexit the system.

FIG. 3 is a schematic diagram of a system for delivering an aerosolaccording to an embodiment of the invention. The context for theembodiment displayed in this figure is a device capable of deliveringdoses of aerosolized drugs. In this embodiment, reservoir 301 is coupledto dose controller 302 via flow channel 304. Dose controller 302,including valve 303, is configured to deliver a metered amount of thecompound to atomizer 305 via flow channel 306. Atomizer 305, uponreceiving the compound, can create an aerosol of the compound anddeliver it to flow path 306, which can be a user interface, or it can beany type of conduit for the aerosol.

In one embodiment, aerosol flow path 306 includes light source 307 andlight detector 308. Light source 307 is configured to send light acrossaerosol flow path 306, either directly or in combination with mirrorsand collimators, or in any practicable way such that scattered light canbe detected by light detector 308. Light detector 308 is placed in sucha way that it can detect light from light source 307, including lightthat has scattered from an aerosol present in aerosol pathway 306.Processor 309, coupled to light detector 308, is further coupled to dosecontroller 302 and can provide a signal to dose controller 302 that isassociated with the light detected at light detector 308.

In one embodiment, aerosol flow path 306 includes pressure sensor 311for detecting pressure inside aerosol flow path 306. Pressure sensor 311can be coupled to processor 309. In this embodiment, processor 309 canuse information received from pressure sensor 311 in providing an outputsignal for feedback to dose controller 302.

In one embodiment, person 310 can receive the aerosol by inserting thedistal end of aerosol flow path 306 into an orifice, and inhaling theaerosol. After delivering the aerosol to person 310, processor 309 isconfigured to receive a signal from light detector 310 and send anoutput signal to dose controller 302. The output signal can includeinformation for metering a subsequent dose or doses.

In another embodiment of the invention, processor 309 is configured toreceive a signal from light detector 308 that is associated with person310 exhaling after inhaling the aerosol. Using the signal associatedwith inhaling and the signal associated with exhaling, processor 309 isconfigured to calculate a comparison of the two signals, and send anoutput signal associated with this comparison to dose controller 302.The output signal can include information for metering a subsequent doseor doses.

FIG. 4 is a block-diagram overview of a method according to anembodiment of the invention. One skilled in the art will recognize thatthe steps described in FIG. 4 need not necessarily be performed in theorder displayed; the steps may be performed in any order practicable.

At step 401, a first aerosol enters a flow path under a first pressure.The first pressure can be caused by, for example, inhalation,exhalation, or any other practicable source for creating pressureappropriate for a given context. At step 402, a light source activatesand light from the light source scatters from a first aerosol. Oneskilled in the art would understand that the light source may not be asingle light source, but can be any appropriate combination of lightsources.

At step 403, a light detector detects the scattered light, and sends alight-detection signal to a processor to process the signal. At step404, the processor receives the light-detection signal.

At step 405, the processor receives from a pressure sensor a signalassociated with the airflow, or any general fluid flow, in the flowpath. The processor, at step 406, can use the received signals tocalculate the amount of the first aerosol that traverses the flow path.

At step 407, a second aerosol enters the flow path under a secondpressure. The second pressure can be caused by, for example, inhalation,exhalation, or any other practicable source for creating a pressureappropriate for a given context. The light source is activated at step408, and light from the light source is scattered from the secondaerosol.

Next, at step 409, the scattered light is detected by the lightdetector, and a detection signal is sent to the processor forprocessing. The signal is received by the processor at step 410, and atstep 411, the processor receives a signal from the pressure sensorassociated with the aerosol flow in the flow path.

The processor, at step 412, can use the received signals to calculatethe amount of the second aerosol that traverses the flow path. At step413, the processor compares the amount of the first aerosol detectedwith the amount of the second aerosol detected, and outputs a signalassociated with the difference between the two at step 414.

FIG. 5 is a block diagram of a method according to an embodiment of theinvention. This method is presented in the context of a person inhalingand exhaling an aerosolized drug. One skilled in the art will recognize,however, that the method is equally applicable in any situation in whicha compound is metered, aerosolized and dispensed under pressure. Oneskilled in the art will further recognize that the steps described inFIG. 4 need not necessarily be performed in the order displayed; thesteps may be performed in any order practicable.

At step 501, initial conditions for depositing the aerosol are set up.In these initial conditions, the compound to be aerosolized exists in areservoir chamber. At this point, the system metering valve is closed,and the light source and light detector for measuring the deposited doseare dormant.

At step 502, a person's lungs expand, thereby creating a pressure regionin the aerosol flow path. A pressure sensor changes in response to thischange in pressure.

At step 503, the person holds his breath and the drug is metered by adose controller. At this point, a valve opens, delivering the drug to anatomizer. At step 504, the person exhales, and the pressure sensorreflects this change in pressure. At this point, light source is active.One skilled in the art will appreciate that steps 502 and 503 can beused to calibrate the system by creating a baseline measurement that canbe subtracted out of subsequent aerosol measurements.

Possible methods of metering include, but are not limited to, using apiston or syringe device, a peristaltic pump. Other possible methodsinclude using acoustic volume sensing (AVS) techniques as described inU.S. Pat. No. 5,575,310, incorporated herein in its entirety, and fluidmanagement system (FMS) techniques as described in U.S. Pat. No.5,193,990, incorporated herein in its entirety.

The aerosol is delivered to the person in step 505. In this step, theperson inhales. The change in pressure is noted by the pressure sensor,and an air valve opens. In this step, the target volume is atomized atan atomizer, and the aerosol flows into an aerosol flow path formeasurement and delivery to the person. The light source is active inthis step, the pressure sensor indicates pressure, and the aerosolvolume of the inhaled aerosol is calculated. In one embodiment, theaerosol is delivered at room temperature. In this step, the person canhold his breath to maximize aerosol deposition in the lungs.

At step 507, the person exhales, causing the pressure sensor to indicateairflow. At this step, the light source is activated and the aerosolvolume of the exhaled aerosol is calculated. Using the calculationsperformed during inhalation and exhalation, at step 508, the targetvolume of the aerosol is adjusted. At step 509, the sequence isrepeated.

In one embodiment of the invention, the method steps of FIG. 5 areembodied as a computer program on a processor readable medium thatstores instructions to cause a processor to perform the steps of themethod.

The foregoing description of the embodiments of the invention has beenpresented only for the purpose of illustration and description and isnot intended to be exhaustive or to limit the invention to the preciseforms disclosed. Numerous modifications and adaptations thereof will beapparent to those skilled in the art without departing from the spiritand scope of the present invention.

What is claimed is:
 1. An apparatus comprising: a light source; adetector operable to detect light; a sensor operable to determine apressure; and a processor coupled to the detector and the sensor, theprocessor configured to receive a signal associated with the detectorthat is associated with a first therapeutic agent introduced into a flowpath; receive a signal from the sensor; and calculate a volume of thefirst therapeutic agent when the processor receives a signal associatedwith the detector, the calculation based on the signal representing thesensor.
 2. The apparatus of claim 1, further comprising wherein theprocessor is further configured to: receive a signal associated with thedetector from a second therapeutic agent introduced into a flow path;receive a signal from the sensor; calculate a volume of the secondtherapeutic agent when the processor receives a signal associated withthe detector, the calculation based on the signal representing thesensor; and output a signal associated with a comparison of the volumeof the first therapeutic agent and the volume of the second therapeuticagent.
 3. The apparatus of claim 2, further comprising dose-selectionmeans coupled to the processor, and wherein the output signal isreceived by the dose-selection means, and wherein the output signalincludes information useful for metering a third therapeutic agent. 4.The apparatus of claim 2, wherein the output signal comprisinginformation for metering a third therapeutic agent.
 5. A therapeuticagent delivery device comprising: a housing having an orifice fordelivery of the therapeutic agent to the user; and a processorconfigured to receive a signal associated with a sensor, the signalassociated with a volume of a first therapeutic agent delivered to theuser; receive a signal associated with the sensor, the signal associatedwith a volume of a second therapeutic agent delivered to the user;calculate a volume of the first therapeutic agent delivered and thesecond therapeutic agent delivered; compare the calculated volumes; andadjust the target volume of a subsequent delivery of the therapeuticagent.
 6. The device of claim 5 further comprising a detector operableto detect light.
 7. The device of claim 5 further comprising a pressuresensor.
 8. The device of claim 7, further comprising wherein theprocessor is further configured to: receive a signal associated with thedetector from a second therapeutic agent introduced into a flow path;receive a signal from the pressure sensor; calculate a volume of thesecond therapeutic agent when the processor receives a signal associatedwith the detector, the calculation based on the signal representing thesensor; and output a signal associated with a comparison of the volumeof the first therapeutic agent and the volume of the second therapeuticagent.
 9. The device of claim 8, further comprising a dose-selectionmeans coupled to the processor, and wherein the output signal isreceived by the dose-selection means, and wherein the output signalincludes information useful for metering a third therapeutic agent. 10.The device of claims 9 wherein the device is configured to deliver apredetermined volume of the therapeutic agent.
 11. A therapeutic agentdevice comprising: a volume transducer, the volume transducer sends asignal associated with a volume of a therapeutic agent in a flow path;and a processor, the processor configured to receive signals from thevolume transducer and calculate the volume of the therapeutic agent, andadjust a target volume of the therapeutic agent.
 12. The device of claim11 further comprising a pressure sensor.
 13. The device of claim 11further comprising a detector operable to detect light.
 14. The deviceof claim 13 further comprising wherein the processor is furtherconfigured to: receive a signal associated with the detector that isassociated with a first therapeutic agent introduced into the flow path;receive a signal from a pressure sensor; and calculate a volume of thefirst therapeutic agent when the processor receives a signal associatedwith the detector, the calculation based on the signal representing thesensor.
 15. The device of claim 14, further comprising wherein theprocessor is further configured to: receive a signal associated with thedetector from a second therapeutic agent introduced into a flow path;receive a signal from the sensor; calculate a volume of the secondtherapeutic agent when the processor receives a signal associated withthe detector, the calculation based on the signal representing thesensor; and output a signal associated with a comparison of the volumeof the first therapeutic agent and the volume of the second therapeuticagent.
 16. The apparatus of claim 15, further comprising dose-selectionmeans coupled to the processor, and wherein the output signal isreceived by the dose-selection means, and wherein the output signalincludes information useful for metering a third therapeutic agent. 17.The apparatus of claim 15, wherein the output signal comprisinginformation for metering a third therapeutic agent.